I know D&D 3.5 pretty well. What are the substantial changes from 3.5 to 4th edition?

Question

I know D&D 3.5 pretty well. What are the substantial changes from 3.5 to 4th edition?

Answer 1

- Power Source, the first PHB will feature Martial, Arcane and Divine.

- Power: At will, per encounter, per day.

- Alignment: LG, Good, Unaligned, Evil, Chaotic Evil

- Role of Character: Leader, Controller, Striker and Defender.

- Unified Attack, Defence and Skills progression.

- many more....

Visit: http://www.enworld.org/index.php?page=4e

You will have all the news of 4E

Answer 2

Huge.  All classes will have standardized powers divided into at will, per encounter and daily powers.  The source of the powers will differ between arcane, divine and martial by class, expect new sources such as psionic to be added eventually.  No matter what your class, you will have the same number of each type of power (though wizards are a slight exception, they know more powers but can only use the same number per day).  

Combat spells are now powers.  Noncombat spells are rituals, which are separate from the powers system.

Combat is more tactical.  Many powers involve moving either the person using the power, his allies or an enemy in some way, using these to set up combat advantages of some sort or to make use of terrain features is a major part of the game.

Encounters are intended to be larger.  A "typical" party of 4 characters is expected to take on 8 monsters of equal level in a standard encounter, of course, a certain amount of mixing and matching is expected.

Magic Items have been completely reworked.  Not having the actual book yet, I don't know much about them, but I do know all items have levels now.  In general characters are expected to be less magic item dependent.

There's a lot more, I'd suggest hitting the Wizards website and checking out the 4e previews or taking a look at the prerelease PHB (compiled from various released materials, reasonably accurate but far from complete)